The long-range goal of this project is to define the biological role of fibronectin (Fn), a plasma and tissue matrix protein, in inflammatory processes. This project addresses two specific subjects: epithelial wound healing and macrophage activation. Fibronectin mediates cell attachment to collagen and fibrin (Fg), binds and activates macrophages and is chemotactic for several cell types. Epithelial cells migrate over a substrate matrix of Fn/Fg in healing corneal and skin wounds. We hypothesize that the molecular form of Fn critically influences these diverse biological effects. We will determine whether this provisional matrix promotes epithelial migration by studying the effects of local application of polyclonal and monoclonal Fab antibody fragments to Fn, Fg and laminin in healing guinea pig corneal wounds in vivo and in vitro (organ culture). We will characterize the molecular form of Fn and Fg in the matrix by SDS-PAGE autoradiography and by antibody blot techniques and use this information to construct substrates for testing epithelial cell attachment in vitro. Monocytes or macrophages recognize, bind and synthesize Fn, yet the biological control of these processes is unknown. Macrophage interaction with Fn will be characterized in three ways. We will analyze (1) the form of Fn recognized by the macrophage by in vivo and in vitro binding studies; (2) the modulation of antigen presentation, collagenase and PGE2 production and tumor killing by different forms of Fn; and (3) the control of Fn synthesis by lymphokines. These studies will employ analytic gel techniques, immunoelectron microscopy, in vivo animal experimentation and in vitro studies of human cells. We expect to learn which forms of Fn are most active in promotion of epithelial wound healing and macrophage activation, which may lead to more effective control of these vital processes in humans.